Our laboratory is investigating ways to improve the efficacy of tumor- infiltrating lymphocytes (TIL), and trying to delineate the mechanisms of their action in vivo. We have been studying the use of cytokine adjuvants incorporated in slow-release collagen matrix to enhance the host antitumor response. We have described that interleukin-6 utilized in this fashion can generate TIL with enhanced in vivo activity. In addition, we are studying the migration of TIL in response to various stimuli. We have recently found that the fresh tumor preparations secrete a soluble substance which is chemoattractant to TIL. We are attempting to identify the product(s) responsible for this, and determine its role in TIL function. These studies are associated with on-going clinical trials trying to determine the role of cyclo-phosphamide in the localization of TIL to sites of tumor. Early data suggest that cyclophosphamide may contribute to successful TIL localization in patients. Other clinical trials have investigated the role of chemotherapy and interleukin-2 in the treatment of colorectal cancer, as well as the benefit of long-term maintenance lymphokine therapy (using PEG-IL2) in the immunotherapy of melanoma and renal cell carcinoma. A new trial investigating autoimmunization with tumor and growth of TIL from these cutaneous inoculation sites is being investigated as a way to improve a patient's immune response against their cancer.